Bladder cancer often develops in people aged fifty and older. Men develop bladder cancer at a rate 2 to 3 times higher than that for women. Also, smokers are approximately four times more likely to develop bladder cancer than nonsmokers.
Bladder cancer is roughly classified into two types, i.e., superficial bladder cancer and infiltrative bladder cancer. Superficial bladder cancer is characterized by shallow papillary tumors that protrude out from the inner surface of the bladder and relatively low malignancy. Superficial bladder cancer can be treated endoscopically, although it recurs in the bladders of half or more patients. In contrast, infiltrative bladder cancer is characterized by deep infiltration, such as the bladder wall, and metastasis to other parts of the body. Infiltrative bladder cancer can be treated by bladder extirpation, chemotherapy, and radiotherapy.
The most common sign of bladder cancer is painless hematuria; however, symptoms may be similar to those of cystitis, such as increased urinary frequency, pain during urination, or the feeling of incomplete emptying of the bladder. Diagnosis of bladder cancer is carried out by urine analysis (cytological diagnosis), x-ray imaging, or endoscopy.
Due to a lack of specific and highly sensitive tumor markers for early diagnosis, such as by assay of urine or blood, bladder cancer is often detected after the cancer has progressed. Accordingly, practical application of a simple detection method with the use of specific and highly sensitive tumor markers for urothelial cancer, and particularly for bladder cancer, is desired.
A variety of markers and methods have been proposed for diagnosis of bladder cancer. Examples include the detection of changes in expression levels of genes, such as nucleophosmin/B23 (JP Patent Publication (kokai) No. 2004-337120 (A)), HURP (JP Patent Publication (kokai) No. 2004-248508 (A)), and CYP4B1 or CYP4B2 (JP Patent Publication (kokai) No. 2002-238599 (A)), the detection of changes in the level of a given protein in urine (JP Patent Publication (kokai) Nos. 2004-61288 (A) and H7-309895 (1995)(A)), and the detection of changes in the level of soluble Fas in blood or urine (JP Patent Publication (kokai) No. 2000-131321 (A); and U.S. Pat. No. 7,759,077). More recently, the detection of an increase in the level of CXCL1 protein (see U.S. Pat. No. 7,910,316), the detection of an increase in the level of 184P1E2 protein (see U.S. Pat. Nos. 7,879,570 and 7,135,549), the detection of the presence of carcinoembryonic antigen (CEA; see U.S. Pat. No. 7,862,997), the detection of an increase in the level of 58P1D12 protein (see U.S. Pat. No. 7,842,458), the detection of the presence of survivin (see U.S. Pat. Nos. 7,794,926 and 7,776,518), the detection of an increase in the level of 213P1F11 (see U.S. Pat. No. 7,563,444), the assay of α-methylacyl-CoA racemase activity (see U.S. Pat. Nos. 7,374,902 and 7,374,897), the detection of an increase in the level of 36P6D5 (see U.S. Pat. No. 7,223,542), the absence of methylthioadenosine phosphorylase (MTAP; see U.S. Pat. No. 7,192,711), the detection of an increase in the level of SIX1 (U.S. Pat. No. 7,153,700), the detection of an increase in the level of nucleophosmin/B23 (see U.S. Pat. No. 7,011,950), the detection of increases in the levels of syndecan-1 and hepatocyte growth factor activator-inhibitor type 2 (see U.S. Pat. No. 6,998,232), the detection of an increase in prostate stem cell antigen (see U.S. Pat. No. 6,960,443), the detection of the presence of BLCA-6 (see U.S. Pat. No. 6,951,926), the detection of the presence of anti-Csk auto-antibodies (see U.S. Pat. No. 6,759,204), the detection of a change in the number of chromosomes 1, 7, 8, 9, 10, 11, Y and/or X (see U.S. Pat. No. 6,573,042), the detection of the level of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor, and/or tryptase in urine (see U.S. Pat. No. 6,008,003), and the detection and quantification of expression of ANXA10, C14orf78, CTSE, CRH, IGF2, KLF9, KRT20, MAGEA3, POSTN, PPP1R14D, SLC1A6, TERT, ASAM, and MCM10 (see European Pat. App. Pub. No. EP 2138848), have been proposed. The detection of aneusomic cells using a probe set consisting of centromeric probes for chromosomes 3, 7 and 17 and the locus-specific probe 9p21 has been proposed as useful for monitoring recurrence and need for continued treatment (see U.S. Pat. No. 7,232,655).
The present disclosure seeks to provide a set of markers, as well as methods of use and a kit, for the detection of bladder cancer, particularly in patients who have symptoms of bladder cancer or have recurrent bladder cancer, and the monitoring of the recurrence of bladder cancer. This and other objects and advantages, as well as inventive features, will become apparent from the detailed description provided herein.